Structural Elucidation of a Polysaccharide from Flammulina velutipes and Its Lipid-Lowering and Immunomodulation Activities.

FVPT1, a novel heteropolysaccharide, was purified from the fruiting body of Flammulina velutipes using magnetic-field-assisted three-phase partitioning and gel permeation chromatography. The structure was characterized using monosaccharide composition and methylation analysis, infrared spectroscopy and nuclear magnetic resonance (NMR). The FVPT1 (~1.64 × 104 Da) was composed of L-fucose, D-galactose, D-glucose and D-mannose at a molar ratio of 1.0:3.5:1.0:1.4. The polysaccharide repeating unit of FVPT1 was established with methylation analyses and NMR spectroscopy. Moreover, a zebrafish larva hyperlipidemia model test demonstrated that FVPT1 can show appreciable lipid-lowering effects. In addition, the FVPT1 exhibited remarkable immunoregulatory activity by increasing nitric oxide, interleukin (IL)-1ß and IL-1 secretion in macrophages. Therefore, these results suggest that FVPT1 has the potential to be developed into a new immune or hypolipidemic health product.

The ERF transcription factor LTF1 activates DIR1 to control stereoselective synthesis of antiviral lignans and stress defense in Isatis indigotica roots.

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

Polysaccharide extracted from cultivated Sanghuangporous vaninii spores using three-phase partitioning with enzyme/ultrasound pretreatment: Physicochemical characteristics and its biological activity in vitro.

Sanghuangporous vaninii, as a valuable dietary supplement and medicinal ingredient, contains abundant bioactive polysaccharides that have health-promoting effects. In the present study, four polysaccharides (SVSPs-C, SVSPs-E, SVSPs-U, and SVSPs-E/U) were extracted for the first time from S. vaninii spores by three-phase partitioning (TPP), enzyme pretreatment before TPP (E-TPP), ultrasonic pretreatment before TPP (U-TPP), and enzyme pretreatment followed by ultrasonic before TPP (E/U-TPP) methods, respectively. Their physicochemical characteristics and in vitro pharmacological functions were determined and compared. Results showed that four TPP-based extraction methods had remarkable impacts on the extraction yield, chemical properties, monosaccharide compositions, and molecular weights (Mw) of SVSPs. Specifically, SVSPs-E/U obtained by E/U-TPP showed the highest extraction yield (25.40 %), carbohydrate content (88.50 %), and the lowest protein content (0.86 %). The four SVSPs had high-Mw (183.8-329.1 kDa) and low-Mw (23.0-156.4 kDa) fractions and mainly consisted of galactose, glucose, and mannose with different contents. In vitro bioactivities assays indicated that SVSPs-E/U possessed stronger antioxidant, hypoglycemic, hypouricemic, immunostimulatory, and antitumor activities than those of SVSPs-C, SVSPs-E, and SVSPs-U. Therefore, our results provide an efficient and promising extraction technique for bioactive polysaccharides from S. vaninii spores, as well as SVSPs had the potential to be applied in functional food, pharmaceutical, and cosmetics fields.

Microbial influence on triggering and treatment of host cancer: An intestinal barrier perspective.

Inflammatory bowel disease (IBD) is associated with complex complications that may lead to tumors. However, research on the mechanisms underlying susceptibility to chronic immune diseases and cancer pathogenesis triggered by the inflammatory environment remains limited. An imbalance in the host gut microbiota often accompanies intestinal inflammation. The delayed recovery of the dysregulated intestinal microbiota may exacerbate systemic inflammatory responses, multiorgan pathology, and metabolic disorders. This delay may also facilitate bacterial translocation. This review examined the relationship between gut barrier disruption and unbalanced microbial translocation and their impact on the brain, liver, and lungs. We also explored their potential roles in tumor initiation. Notably, the role of the intestinal microbiota in the development of inflammation is linked to the immune surveillance function of the small intestine and the repair status of the intestinal barrier. Moreover, adherence to a partially anti-inflammatory diet can aid in preventing the malignant transformation of inflammation by repairing the intestinal barrier and significantly reducing inflammation. In conclusion, enhancing intestinal barrier function may be a novel strategy for preventing and treating chronic malignancies in the intestine and other body areas.

Recent Advances in the Preparation, Structure, and Biological Activities of ß-Glucan from Ganoderma Species: A Review.

Ganoderma has served as a valuable food supplement and medicinal ingredient with outstanding active compounds that are essential for human protection against chronic diseases. Modern pharmacology studies have proven that Ganoderma ß-d-glucan exhibits versatile biological activities, such as immunomodulatory, antitumor, antioxidant, and antiviral properties, as well as gut microbiota regulation. As a promising polysaccharide, ß-d-glucan is widely used in the prevention and treatment of various diseases. In recent years, the extraction, purification, structural characterization, and pharmacological activities of polysaccharides from the fruiting bodies, mycelia, spores, and fermentation broth of Ganoderma species have received wide attention from scholars globally. Unfortunately, comprehensive studies on the preparation, structure and bioactivity, toxicology, and utilization of ß-d-glucans from Ganoderma species still need to be further explored, which may result in limitations in future sustainable industrial applications of ß-d-glucans. Thus, this review summarizes the research progress in recent years on the physicochemical properties, structural characteristics, and bioactivity mechanisms of Ganoderma ß-d-glucan, as well as its toxicological assessment and applications. This review is intended to provide a theoretical basis and reference for the development and application of ß-d-glucan in the fields of pharmaceuticals, functional foods, and cosmetics.

Circulating antigen-primed cytotoxic T-cells in patients with renal tumors treated with surgery.

INTRODUCTION: Systemic immunotherapy has changed the paradigm of treatment of advanced renal cell carcinoma, but nephrectomy continues to benefit selected patients. While we continue to identify mechanisms behind drug resistance, the effect of surgery on natural anti-tumor immunity is poorly understood. Specifically, peripheral blood mononuclear cell (PBMC) profile and tumor reactive cytotoxic T lymphocytes changes secondary to tumor resection have not been extensively characterized. Hence, we aimed to evaluate the effect of nephrectomy on PMBC profile and circulating antigen-primed CD8+ T-cells for patients undergoing solid renal mass resection. METHODS: Patients with localized or metastatic solid renal masses who underwent nephrectomy from 2016 to 2018 were enrolled. Blood samples were collected at 3 timepoints for PBMCs analysis (pre-op, 1 day, and 3 months post-op). Flow cytometry was used to identify CD11ahigh CD8+ T lymphocytes that were then further characterized according to the expression of CX3CR1/GZMB, Ki67, Bim, and PD-1. Changes in circulating CD8+ T-cells from pre-op to 1 day and 3 months post-op were evaluated using Wilcoxon signed rank tests. RESULTS: Antigen-primed CX3CR1+GZMB+ T-cells significantly increased by 3 months after surgery among patients with RCC (0.8 × 109 cells; P = 0.01). In contrast, there was a decrease in absolute numbers of Bim+ T-cells at 3 months (-1.9 × 109 cells; P = 0.02). There were no significant absolute changes in PD-1+ (-1.4 × 109; P = 0.7) and CD11ahigh CD8+ T lymphocytes (1.3 × 109; P = 0.9). Ki67+ T-cells decreased by 3 months (-0.8 × 109; P < 0.001). CONCLUSIONS: Nephrectomy is associated with an increase in cytolytic antigen-primed CD8+ T-cells and specific PBMC profile changes. Further studies are warranted to ascertain the role surgery may have in the restoration of anti-tumor immunity.

A Novel PD-L1 Antibody Promotes Antitumor Function of Peripheral Cytotoxic Lymphocytes after Radical Nephrectomy in Patients with Renal Cell Carcinoma.

The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians because no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex vivo functional assay that measures the tumor cell killing ability of patient-derived CD8 T and NK cells (referred to as "cytotoxic lymphocytes," or CLs) isolated from the peripheral blood of patients with renal cell carcinoma. Patient-derived PBMCs were isolated before and after nephrectomy from patients with renal cell carcinoma. We compared the efficacy of U.S. Food and Drug Administration (FDA)-approved PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab) and a newly developed PD-L1 inhibitor (H1A Ab) in eliciting cytotoxic function. CL activity was improved at 3 mo after radical nephrectomy compared with baseline, and it was associated with higher circulating levels of tumor-reactive effector CD8 T cells (CD11ahighCX3CR1+GZMB+). Treatment of PBMCs with FDA-approved PD-1/PD-L1 inhibitors enhanced tumor cell killing activity of CLs, but a differential response was observed at the individual-patient level. H1A demonstrated superior efficacy in promoting CL activity compared with FDA-approved PD-1/PD-L1 inhibitors. PBMC immunophenotyping by mass cytometry revealed enrichment of effector CD8 T and NK cells in H1A-treated PBMCs and immunosuppressive regulatory T cells in atezolizumab-treated samples. Our study lays the ground for future investigation of the therapeutic value of H1A as a next-generation immune checkpoint inhibitor and the potential of measuring CTL activity in PBMCs as a tool to predict individual response to immune checkpoint inhibitors in patients with advanced renal cell carcinoma.

Construction of Probiotic Double-Layered Multinucleated Microcapsules Based on Sulfhydryl-Modified Carboxymethyl Cellulose Sodium for Increased Intestinal Adhesion of Probiotics and Therapy for Intestinal Inflammation Induced by Escherichia coli O157:H7.

The decreased number of viable bacteria and the ability of Bifidobacterium to adhere to and colonize the gut in the gastrointestinal environment greatly limit their efficacy. To solve this problem, thiolated carboxymethyl cellulose sodium (CMC) probiotic double-layered multinucleated microcapsules with Bifidobacterium adolescentis FS2-3 in the inner layer and Bacillus subtilis SN15-2 embedded in the outer layers were designed. First, the viable counts and release rates of microcapsules were examined by in vitro simulated digestion assays, and it was found that microcapsules were better protected from gastrointestinal digestion than the controls. Compared with free Bifidobacterium strains, double-layered multinucleated microcapsules have higher viable bacterial survival rates and storage stability. Second, through in vitro rheology, tensile tests, isotherm titration calorimetry, and adhesion tests, it was observed that thiolated CMC could enhance the strong interaction of Bifidobacterium with intestinal mucus and significantly promote the proliferation and growth of probiotics. Finally, double-layered multinucleated microcapsules containing B. adolescentis FS2-3 and B. subtilis SN15-2 modified with sulfhydryl-modified CMC were studied in the intestine. Alleviation of Escherichia coli O157:H7 induced intestinal inflammation. The results showed that microencapsulation could significantly increase the colon content of Bifidobacterium, relieve intestinal inflammation symptoms in mice with bacterial enteritis, and repair the intestinal microbiota disorder caused by inflammation. The probiotic double-layered multinucleated microcapsules prepared in this study can improve the survival rate of probiotics and promote proliferation, adhesion, and colonization of probiotics.

A Novel Strain Breeding of Ganoderma lucidum UV119 (Agaricomycetes) with High Spores Yield and Strong Resistant Ability to Other Microbes' Invasions.

The spore powder of Ganoderma lucidum (G. lucidum) has been proven to have a variety of pharmacological activities, and it has become a new resource for the development of health products and pharmaceuticals. However, the scarcity of natural resources, strict growth conditions and difficulty in controlling the stable yield, and quality of different culture batches seriously limit the development and utilization of G. lucidum spore powder. In the present study, the strain with the highest spore powder yield, G0109, was selected as the original strain to generate mutants of G. lucidum using ultraviolet ray irradiation. A total of 165 mutagenic strains were obtained, and fifty-five strains were chosen for the cultivation test. Importantly, one mutagenic strain with high spore powder yield and strong resistance to undesired microorganisms was acquired and named strain UV119. More cultivations demonstrated that the fruiting body and basidiospore yields from UV119 were, respectively, 8.67% and 19.27% higher than those of the parent (G0109), and the basidiospore yield was 20.56% higher than that of the current main cultivar "Longzhi No.1". In conclusion, this study suggested that ultraviolet ray irradiation is an efficient and practical method for Ganoderma strain improvement and thus provided a basis for the development and application of G. lucidum spore production and outstanding contributions to the rapid development of the G. lucidum industry.

Understanding Suboptimal Response to Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs), as a novel class of anticancer therapy, can be more efficacious and less toxic than chemotherapy, but their clinical success is confined to certain tumor types. Elucidating their targets, mechanisms and scope of action, and potential synergism with chemotherapy and/or targeted therapies are critical to widen their clinical indications. Treatment response to an ICI targeting programmed death-1 (anti-PD-1) is sought to be understood here by conducting a preplanned correlative analysis of a phase II clinical trial in patients with small bowel adenocarcinoma (SBA). The cytolytic capacity of circulating immune cells in cancer patients using a novel ex vivo cytotoxicity assay is evaluated, and the utility of circulating biomarkers is investigated to predict and monitor the treatment effect of anti-PD-1. Baseline expression of Bim and NKG7 and upregulation of CX3CR1 in circulating T cells are associated with the clinical benefit of anti-PD-1 in patients with SBA. Overall, these findings suggest that the frequency and cytolytic capacity of circulating, effector immune cells may differentiate clinical response to ICIs, providing a strong rationale to support immune monitoring using patient peripheral blood.

Recent advances in research on Allium plants: functional ingredients, physiological activities, and applications in agricultural and food sciences.

Fruits and vegetables (FVs) have long been a major source of nutrients and dietary phytochemicals with outstanding physiological properties that are essential for protecting humans from chronic diseases. Moreover, the growing demand of consumers for nutritious and healthy foods is greatly promoting the increased intake of FVs. Allium (Alliaceae) is a perennial bulb plant genus of the Liliaceae family. They are customarily utilized as vegetable, medicinal, and ornamental plants and have an important role in agriculture, aquaculture, and the pharmaceutical industry. Allium plants produce abundant secondary metabolites, such as organosulfur compounds, flavonoids, phenols, saponins, alkaloids, and polysaccharides. Accordingly, Allium plants possess a variety of nutritional, biological, and health-promoting properties, including antimicrobial, antioxidant, antitumor, immunoregulatory, antidiabetic, and anti-inflammatory effects. This review aims to highlight the advances in the research on the bioactive components, physiological activities and clinical trials, toxicological assessment for safety, and applications of different Allium plants. It also aims to cover the direction of future research on the Allium genus. This review is expected to provide theoretical reference for the comprehensive development and utilization of Allium plants in the fields of functional foods, medicine, and cosmetics.

Profiling of phytohormone-specific microRNAs and characterization of the miR160-ARF1 module involved in glandular trichome development and artemisinin biosynthesis in Artemisia annua.

MicroRNAs (miRNAs) play crucial roles in plant development and secondary metabolism through different modes of sequence-specific interaction with their targets. Artemisinin biosynthesis is extensively regulated by phytohormones. However, the function of phytohormone-responsive miRNAs in artemisinin biosynthesis remains enigmatic. Thus, we combined the analysis of transcriptomics, small RNAs, and the degradome to generate a comprehensive resource for identifying key miRNA-target circuits involved in the phytohormone-induced process of artemisinin biosynthesis in Artemisia annua. In total, 151 conserved and 52 novel miRNAs and their 4132 targets were determined. Based on the differential expression analysis, miR160 was selected as a potential miRNA involved in artemisinin synthesis. Overexpressing MIR160 significantly impaired glandular trichome formation and suppressed artemisinin biosynthesis in A. annua, while repressing its expression resulted in the opposite effect, indicating that miR160 negatively regulates glandular trichome development and artemisinin biosynthesis. RNA ligase-mediated 5' RACE and transient transformation assays showed that miR160 mediates the RNA cleavage of Auxin Response Factor 1 (ARF1) in A. annua. Furthermore, ARF1 was shown to increase artemisinin synthesis by activating AaDBR2 expression. Taken together, our results reveal the intrinsic link between the miR160-ARF1 module and artemisinin biosynthesis, and may expedite the innovation of metabolic engineering approaches for high and stable production of artemisinin in the future.

A pectic polysaccharide from fresh okra (Abelmoschus esculentus L.) beneficially ameliorates CCl4-induced acute liver injury in mice by antioxidation, inhibition of inflammation and modulation of gut microbiota.

Okra [Abelmoschus esculentus (Linn.) Moench], as a well-known medicinal and food plant, has important physiological activities and health benefits, and polysaccharide is its main bioactive component. In this study, a pectic polysaccharide (OPS-50) prepared from fresh okra pods by three-phase partitioning and gradient (NH4)2SO4 precipitation at a saturation of 50% was employed in carbon tetrachloride (CCl4)-caused acute liver damage in mice to evaluate the hepatoprotective potential. Results indicated that OPS-50 was mainly composed of a limited linear homogalacturonan backbone and abundant rhamnogalacturonan-I domains as side chains. OPS-50 exerted positively protective effects on acute liver damage induced by CCl4 in mice through relieving weight reduction and organ damage, ameliorating liver function and dyslipidemia, alleviating oxidative stress, suppressing pro-inflammatory cytokines, modulating gut microbiota, and promoting short-chain fatty acid secretion. Moreover, liver histopathology demonstrated the protective benefit of OPS-50 on CCl4-caused acute liver damage in mice. Therefore, our data suggested that the pectic OPS-50, as a dietary supplement, have great potential in preventing and treating chemical liver damages.

Bioactive Compounds from Medicinal Mushrooms.

Research progress of active compounds and biological activities of medicinal mushroom-Ganoderma spp., Hericium spp., Phellinus spp., and Cordyceps spp. were summarized systematically. The main active compounds of medicinal mushrooms included are polysaccharides, proteins, triterpenes, meroterpenoids, polyphenols and nitrogen-containing compounds. The biological activities of the compounds cover immunomodulatory activity, antitumor activity, hypoglycemic activity, hepatoprotective activity, and activity of regulation of intellectual flora.

Pulsed Light Mutagenesis of the Willow Bracket Mushroom, Phellinus igniarius (Agaricomycetes), for Enhanced Production of Flavonoids, Laccase, and Fermentation Biomass.

Phellinus igniarius is a medicinal fungus possessing potent therapeutic activity due to the polysaccharides, polyphenols, flavonoids, and other secondary metabolites they contain. Laccases are crucial enzymes involved in lignin degradation in Ph. igniarius and offer great potential to accomplish several bioprocesses. To generate Ph. igniarius strains with high biomass, flavonoid, and laccase activity, we used pulsed light (PL) technology for mutagenesis of Ph. igniarius protoplasts and screened for mutants with high biomass, flavonoid, and laccase activity. At the irradiation power of 100 J, treated distance 8.5 cm, irradiation frequency was 0.5 s/time, three times treatments, after five generations of selection, three mutants were obtained with higher biomass production. Compared with control, the mycelium biomass and the flavonoid production of the screened mutant strain QB72 were increased 20.87% and 53.51%, respectively. The total amount of the accumulated extracellular laccase of the QB72 in the first 6 and 8 days increased 23.38% and 22.37% respectively, and over the total 16 days it increased 9.62%. In addition, RAPD analysis results indicated that the genetic materials of the mutant QB72 were altered. PL mutagenesis method has great potential for developing strains, especially Phellinus.

Isolation of a New Polysaccharide from Dandelion Leaves and Evaluation of Its Antioxidant, Antibacterial, and Anticancer Activities.

Dandelion, in China, has a long history as a medicinal and edible plant, and possesses high nutritional and medical value. The present study aimed to isolate a new polysaccharide (DLP-3) from dandelion leaves and to evaluate its antioxidant, antibacterial, and anticancer activities. The structure of DLP-3 was analyzed using HPLC, FT-IR, SEM, GC-MS, and NMR spectroscopy. DLP-3 mainly consisted of Man, Rha, GlcA, Glc, Gal, and Ara with molar ratios of 2.32, 0.87, 1.21, 3.84, 1.00, and 1.05, respectively, with a molecular weight of 43.2 kDa. The main linkages of DLP-3 contained (1→4)-α-d-Glc, (1→4,6)-α-d-Glc, (1→6)-α-d-Gal, (1→2)-α-d-Man, (1→4)-α-d-Man, ß-l-Ara-(1→, and α-l-Rha-(1→. DLP-3 exhibited a smooth surface, purely flake-like structure, and a triple helix conformation. Moreover, DLP-3 presented obvious antioxidant and antibacterial activities in a concentration-dependent manner. DLP-3 showed significant anticancer activities by inhibiting tumor cell proliferation. These findings provide a theoretical basis for the application of DLP-3 as a natural functional active substance in functional foods.

Recent advances in the bioactive polysaccharides and other key components from Phellinus spp. and their pharmacological effects: A review.

Phellinus spp. is one of the largest genera of Hymenochaetaceae with approximately 220 species, such as P. vaninii, P. buamii, P. linteus, and P. igniarius, these species are considered as precious food supplements and medicinal ingredients in China, Korea, Japan, and other Asian countries for over 2000 years. Phellinus spp. contains abundant bioactive polysaccharides and other key components (e.g., phenolics, terpenes, steroids, etc.). Pharmacological investigations have confirmed that bioactive polysaccharides and other important secondary metabolites from Phellinus spp. possess multiple health-promoting benefits, including antitumor, immunomodulatory, anti-inflammatory, antidiabetic, antioxidant, and antimicrobial effects. However, comprehensive evaluations on the preparation and structural characteristics, bioactivities, and toxicology of these functional components (e.g., polysaccharides, phenolics, terpenes, steroids) from various Phellinus spp. species are very limited, which may restrict the practical application of Phellinus spp. This review summarizes the physicochemical characteristics, pharmacological activities, and possible mechanisms of bioactive components from Phellinus spp. according to published studies from 2017 to 2022. It also surveyed the toxicological assessment for safety and applications of different Phellinus spp. species. This review aims to provide useful references and promising directions for the comprehensive development and utilization of Phellinus spp. in functional foods, pharmaceuticals, and cosmetics.

Corrigendum: Anti-cancer potential of polysaccharide extracted from Polygonatum sibiricum on HepG2 cells via cell cycle arrest and apoptosis.

[This corrects the article DOI: 10.3389/fnut.2022.938290.].

Triple-Negative Breast Cancer Analysis Based on Metabolic Gene Classification and Immunotherapy.

Triple negative breast cancer (TNBC) has negative expression of ER, PR and HER-2. TNBC shows high histological grade and positive rate of lymph node metastasis, easy recurrence and distant metastasis. Molecular typing based on metabolic genes can reflect deeper characteristics of breast cancer and provide support for prognostic evaluation and individualized treatment. Metabolic subtypes of TNBC samples based on metabolic genes were determined by consensus clustering. CIBERSORT method was applied to evaluate the score distribution and differential expression of 22 immune cells in the TNBC samples. Linear discriminant analysis (LDA) established a subtype classification feature index. Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were generated to validate the performance of prognostic metabolic subtypes in different datasets. Finally, we used weighted correlation network analysis (WGCNA) to cluster the TCGA expression profile dataset and screen the co-expression modules of metabolic genes. Consensus clustering of the TCGA cohort/dataset obtained three metabolic subtypes (MC1, MC2, and MC3). The ROC analysis showed a high prognostic performance of the three clusters in different datasets. Specifically, MC1 had the optimal prognosis, MC3 had a poor prognosis, and the three metabolic subtypes had different prognosis. Consistently, the immune characteristic index established based on metabolic subtypes demonstrated that compared with the other two subtypes, MC1 had a higher IFNγ score, T cell lytic activity and lower angiogenesis score, T cell dysfunction and rejection score. TIDE analysis showed that MC1 patients were more likely to benefit from immunotherapy. MC1 patients were more sensitive to immune checkpoint inhibitors and traditional chemotherapy drugs Cisplatin, Paclitaxel, Embelin, and Sorafenib. Multiclass AUC based on RNASeq and GSE datasets were 0.85 and 0.85, respectively. Finally, based on co-expression network analysis, we screened 7 potential gene markers related to metabolic characteristic index, of which CLCA2, REEP6, SPDEF, and CRAT can be used to indicate breast cancer prognosis. Molecular classification related to TNBC metabolism was of great significance for comprehensive understanding of the molecular pathological characteristics of TNBC, contributing to the exploration of reliable markers for early diagnosis of TNBC and predicting metastasis and recurrence, improvement of the TNBC staging system, guiding individualized treatment.

Anti-cancer Potential of Polysaccharide Extracted From Polygonatum sibiricum on HepG2 Cells via Cell Cycle Arrest and Apoptosis.

Polygonatum sibiricum is one of the most widely used traditional Chinese medicine in China. Polygonatum sibiricum polysaccharide (PSP) is the main functional component of Polygonatum sibiricum. In this study, a water-soluble polysaccharide (PSP-1) was first isolated from Polygonatum sibiricum with a molecular weight of 38.65 kDa. Structural analysis was performed via methylation and FT-IR spectroscopy analyses, which in combination with NMR spectroscopy, revealed that PSP-1 has a → 4-α-D-Glcp-1 → backbone with the substitution at O-6 with the ß-D-Glcp-1 → residues. Furthermore, PSP-1 exhibited potent and concentration-dependent anticancer effects, inducing HepG2 cell apoptosis and arresting the cell cycle at the G1 phase. Moreover, PSP-1 also decreased the mitochondrial membrane potential, damaged the nucleus of HepG2 cells, and increased the activity of caspase-9 and-3 in the intrinsic apoptotic pathways to induce HepG2 cell apoptosis. To conclude, PSP-1 might be a good candidate for the treatment of liver cancer, and this work provides important information for understanding the relationship between structure and antitumor activity of PSP-1, which is relevant for the treatment of hepatocellular carcinoma in clinic.